Sanofi-Aventis’ worst fears have been realised with the news that a US regulator’s advisory panel has voted unanimously against recommending approval of the company’s obesity pill Acomplia, leading to a share decline this morning of over 6%.
The US Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee voted 14-0 against approving Acomplia (rimonabant) in combination with diet and exercise, for the treatment of chronic obesity, or for people who are overweight with at least one risk factor for heart disease. The panel said that the benefits do not outweigh the risk of psychiatric adverse effects seen in patients taking the drug, including suicide and seizures.
Sanofi issued a statement saying that it plans to “work closely with the FDA to address the committee’s recommendations” before the agency makes its final decision scheduled for July 26. However it hardly ever goes against the advice of its panels so the likelihood of the drug hitting the US market, where it would have been sold as Zimulti, in the near future are pretty much zero.
The committee reviewing the company’s application found that while 20mg of Acomplia did result in significant weight loss, people who took the treatment were twice as likely to have thoughts of suicide as those on placebo. Three patients on the drug killed themselves during clinical trials, Sanofi stated, while a fourth suicide reported after it was approved in Europe in June 2006, has yet to be confirmed.
Amy Egan, an FDA staff medical reviewer, said that “the numbers of events are small, but in aggregate they are worrisome,” and disagreed with the Franco-German drugmaker’s claim that the increase in cases of psychiatric adverse events were attributable to depression or other disorders not directly caused by Acomplia. “We strongly believe that it is causal,” she said, noting that 88% of patients who reported psychiatric problems when taking the treatment did not have a history of depression.
Sanofi had recommended that patients be screened for depression before being prescribed Acomplia and advised that patients should visit their doctors five times during the first year of treatment to be reassessed, but this did not convince the committee. Indeed, Ms Egan’s fears were echoed by panellist Jules Hirsch, a professor at Rockefeller University in New York, who said that “there is a reasonable suspicion that we better learn some more and watch this affair more closely before we launch into use of the drug”.
The fact that approval is highly unlikely in the USA is a serious blow for Sanofi which had previously hoped that Acomplia would be a blockbuster, and a big one at that, given that a third of American adults are deemed to be clinically obese. The decision also suggests a hardening of attitudes at the FDA towards new drugs, especially in the present climate where the agency seems to be under constant attack from pressure groups and the politicians who believe it has granted approvals far too easily in the past.
